New dihydro and tetrahydro derivatives of desmycosin. III. The opening of oxirane ring of 12,13-epoxydesmycosin.

Opening the oxirane ring of 12,13-epoxydesmycosin dimethylacetal (1) by catalytic hydrogenation gave the 10,11-dihydro-12,13-epoxy derivative (3) as the main product. Reductive oxirane cleavage was accomplished with dissolved metal (Zn) giving the 10,13-dihydro-13-hydroxy compound (6). Mild acid hydrolysis of 6 gave expected 10,13-dihydro-13-hydroxydesmycosin (8), but hydrolysis of 3, under the same conditions, gave three tautomeric desepoxy products.

Prevention of necrotic enteritis in piglets by vaccination of pregnant gilts with a Clostridium perfringens type C and D bacterin-toxoid.

On a large pig farm with a known history of necrotic enteritis 12 pregnant gilts were vaccinated s. c. 7 and 2 weeks before expected farrowing with a commercial bacterin-toxoid preparation of toxigenic strains C. perfringens type C and D (DizevakR-Pliva, Zagreb). At the farrowing the titers of beta-antitoxins in serum samples from vaccinated gilts ranged from 9.0 to 26.0 IU/ml with a mean value of 14.16 IU/ml. Colostral titers varied from 12.0 IU/ml with a mean of 16.12 IU/ml. On the second day of life the mean serum titers between litters differed greatly from 4.75 to 24.0 IU/ml. By the age of 7 days the average serum titers were commonly lower and varied between the litters from 2.25 to 15.0 IU/ml, with a low of 1.5 to a high of 16.0 IU/ml in single animals. Ten (8.47%) out of a total of 118 piglets from vaccinated gilts died during the first 7 days of life but the losses were not caused by C. perfringens infection. In unvaccinated control animals 18 (15.9%) of 113 piglets died, eleven of them with clinical and pathoanatomical signs of necrotic enteritis. The affected piglets predominantly succumbed in the first 4 days of life. These data indicate that the investigated bacterin-toxoid can be successfully used in immunoprophylaxis of necrotic enteritis in piglets.

Susceptibility to antimicrobial agents of Streptococcus suis capsular type 2 strains isolated from pigs.

The minimal inhibitory concentrations (MICs) for thirty-three epidemiologicaly unrelated clinical isolates of Streptococcus suis capsular type 2 were determined in relation to ampicillin, ampicillin-sulbactam, amoxicillin, clavulanate-amoxicillin, penicillin G, cephalexin, gentamicin, streptomycin, erythromycin, tylosin and doxycycline, using the microtitre broth dilution procedure described by the U.S. National Committee for Clinical Laboratory Standards (NCCLS). Gentamicin was the most active compound tested, with an MIC for 90% of the strains tested (MIC(90)) of 0.4 mg/L. Overall, 70% of strains were resistant to doxycycline (MIC(90) > or = 100.0 mg/L), followed by penicillin G (51% of strains) (MIC(90) + or = 100.0 mg/L). Resistance to amoxicillin and ampicillin was 36.4% (MIC(90) 12.5 mg/L) and 33.3% (MIC(90) 50.0 mg/L), respectively. 15.2% of S. suis strains were resistant to streptomycin, tylosin and cephalexin with MIC90 values of 25.0 mg/L, 12.5 mg/L and 25.0 mg/L, respectively. A combination of ampicillin and sulbactam (MIC(90) 6.3 mg/L) and a combination of amoxicillin and clavulanate (MIC(90) 3.1 mg/L) as well as erythromycin (1.6 mg/L) were of the same efficacy, with a total of 9.1% resistant S. suis strains. This high percentage of resistance to doxycycline and penicillin G precludes the use of these antibiotics as empiric therapy of swine diseases.

10,11,12,13-Tetrahydro derivatives of tylosin. II. Synthesis, antibacterial activity and tissue of 4'-deoxy-10,11,12,13-tetrahydrodesmycosin.

4'-Deoxy-10,11,12,13-tetrahydrodesmycosin was prepared in six-step reactions. Antibacterial screening shows retained antibacterial spectrum of tylosin with some improvement against tylosin-sensitive Staphylococci and Haemophilus influenze. However, the pharmacokinetic data demonstrated rapid distribution from blood in tissues and prolonged maintenance in all tissues, especially in the lungs, in comparison with tylosin.

Structure-activity relationship among polyhydro derivatives of tylosin.

Tetra-, hexa- and octahydro derivatives of tylosin were prepared by the reduction of the conjugated double bond and carbonyl groups. Hydrogenation of the diene did not change the in vitro antimicrobial activity of compounds, while reduction of carbonyls causes small or complete loss of activity.

9a,11-cyclic carbamates of 15-membered azalides.

The novel 9a,11-cyclic carbamates (13-15) of 9-deoxo-9a-aza-9a-homoerythromycin A (4) have been prepared and characterized by 1H-1H and 1H-13C 2D NMR spectroscopy. When compared to azithromycin (1) or its 6-O-methyl derivative (2), the new bicyclic 15-membered azalides exhibited substantially decreased antibacterial activities in vitro.